Faculty Bibliography

Platelet markers [soluble CD40 ligand (sCD40L) and soluble p selectin (sPselectin)] are associated with platelet activation and cardiovascular events. We sought to investigate the reproducibility of these markers over time and the effect of low-dose aspirin on sCD40L and sPselectin in plasma and serum. Following an overnight fast, 40 healthy volunteers had weekly phlebotomy and were administered aspirin 81 mg/day between weeks 3 and 4. Reproducibility over time was assessed by coefficient of variation (CV) and inter-class correlation coefficient. Correlation between markers was assessed using Pearson r statistic. Difference between levels pre- and post-aspirin was measured with Wilcoxon signed-rank test. Data are presented as median (interquartile range). sCD40L and sPselectin measurements were reproducible over time in plasma and serum (CV < 10 %). Measurement of sCD40L and sPselectin in plasma correlated with levels in serum before aspirin and after aspirin. There was no significant correlation between sCD40L and sPselectin. After 1-week of aspirin 81 mg/day, there was a reduction in sCD40L and sPselectin in serum and plasma, respectively. Soluble CD40L and sPselectin are independent markers that are reproducible over time in both plasma and sera and are reduced by 1-week of low-dose aspirin.

Myocardial necrosis in the perioperative period of noncardiac surgery is associated with short-term mortality, but long-term outcomes have not been characterized. We investigated the association between perioperative troponin elevation and long-term mortality in a retrospective study of consecutive subjects who underwent hip, knee, and spine surgery. Perioperative myocardial necrosis and International Classification of Disease, Ninth Revision-coded myocardial infarction (MI) were recorded. Long-term survival was assessed using the Social Security Death Index database. Logistic regression models were used to identify independent predictors of long-term mortality. A total of 3,050 subjects underwent surgery. Mean age was 60.8 years, and 59% were women. Postoperative troponin was measured in 1,055 subjects (34.6%). Myocardial necrosis occurred in 179 cases (5.9%), and MI was coded in 20 (0.7%). Over 9,015 patient-years of follow-up, 111 deaths (3.6%) occurred. Long-term mortality was 16.8% in subjects with myocardial necrosis and 5.8% with a troponin in the normal range. Perioperative troponin elevation (hazard ratio 2.33, 95% confidence interval 1.33 to 4.10) and coded postoperative MI (adjusted hazard ratio 3.51, 95% confidence interval 1.44 to 8.53) were significantly associated with long-term mortality after multivariable adjustment. After excluding patients with coronary artery disease and renal dysfunction, myocardial necrosis remained associated with long-term mortality. In conclusion, postoperative myocardial necrosis is common after orthopedic surgery. Myocardial necrosis is independently associated with long-term mortality at 3 years and may be used to identify patients at higher risk for events who may benefit from aggressive management of cardiovascular risk factors.

Experimental and epidemiological studies suggest that vitamin D may be implicated in haemostatic regulations and influence the risk of venous thromboembolism (VTE). The aim of this study was to investigate whether oral supplementation of vitamin D3 combined with calcium reduces the risk of VTE. In the randomised, double-blind, placebo-controlled Women's Health Initiative Calcium Plus Vitamin D trial, 36,282 postmenopausal women aged 50-79 years were randomised to receive 1,000 mg of calcium carbonate and 400 IU of vitamin D3 per day (n=18,176) or a matching placebo (n=18,106) during an average of seven years. This secondary analysis of the trial compared the incidence of VTE by treatment group using an intention-to-treat Cox regression analysis. The incidence of VTE did not differ between women randomised to calcium plus vitamin D and women randomised to placebo (320 vs 348 VTE events, respectively; hazard ratio (HR) 0.92, 95 % confidence interval (CI) 0.79-1.07). Results were not modified in an analysis using inverse-probability weights to take non-adherence into account (HR 0.94, 95 %CI 0.73-1.22) or in multiple subgroups. Whereas the risk of a non-idiopathic VTE was similar between groups, the risk of idiopathic VTE was lower in women randomised to calcium plus vitamin D (40 vs 65 events; HR 0.62, 95 %CI 0.42-0.92). In conclusion, daily supplementation with 1,000 mg of calcium and 400 IU of vitamin D did not reduce the overall incidence of VTE in generally healthy postmenopausal women. However, the observed reduced risk of idiopathic VTE in women randomised to calcium and vitamin D warrants further investigations.